Response to netakimab in radiographic axial spondyloarthritis patients with different baseline C-reactive protein, sacroiliitis evaluated by MRI and peripheral joint involvement status: a post-hoc analysis of the ASTERA study.

OBJECTIVES: Netakimab is a humanised camelid-derived monoclonal antibody targeting interleukin-17A. Here, we report the results of post-hoc analysis of the ASTERA phase 3 study (NCT03447704, February 27, 2018) in patients with active radiographic axial spondyloarthritis (r-axSpA) grouped by baseline C-reactive protein (CRP), baseline sacroiliac joint (SIJ) inflammation through magnetic resonance imaging (MRI) or presence of peripheral arthritis (PA). METHODS: In this double-blinded, multicentre, randomised, placebo-controlled, phase 3 ASTERA study, 228 adult patients with active r-axSpA received 120 mg of subcutaneous netakimab or placebo at weeks 0, 1, 2, and thereafter every other week. For the subanalysis, 16-week data of 114 netakimab-treated patients with the available baseline CRP and SIJ MRI were grouped by normal (<5 mg/L) or abnormal (≥5 mg/L) CRP, by the grade of sacroiliitis (SI) based on the SPARCC MRI score <2 (MRI-SI-) or ≥2 (MRI-SI+), or by the presence of PA. ASAS-recommended activity, spinal mobility, and function endpoints for r-axSpA were analysed. RESULTS: At week 16, an improvement in all the outcomes was similar for MRI-SI- and MRI-SI+ patients, except for a change in ASspi-MRI-a which was significantly greater in MRI-SI+. Netakimab was effective regardless of baseline CRP and PA. For patients with CRP ≥5 mg/L, a more pronounced decline in r-axSpA activity was observed with a trend towards the most prominent improvement in ASDAS-CRP and BASDAI for patients with CRP >20 mg/L. CONCLUSIONS: Subcutaneous netakimab is effective in patients with r-axSpA irrespective of baseline CRP and inflammation on SIJ MRI. The benefit in patients with high CRP (>20 mg/L) was more pronounced.

The efficacy and safety of levilimab in severely ill COVID-19 patients not requiring mechanical ventilation: results of a multicenter randomized double-blind placebo-controlled phase III CORONA clinical study.

OBJECTIVE AND DESIGN: The aim of this double-blind, placebo-controlled, phase III CORONA clinical trial was to evaluate the efficacy and safety of IL-6 receptor inhibitor levilimab (LVL) in subjects with severe COVID-19. SUBJECTS: The study included 217 patients. The eligible were men and non-pregnant women aged 18 years or older, hospitalized for severe COVID-19 pneumonia. TREATMENT: 206 subjects were randomized (1:1) to receive single subcutaneous administration of LVL 324 mg or placebo, both in combination with standard of care (SOC). 204 patients received allocated therapy. After the LVL/placebo administration in case of deterioration of symptoms, the investigator could perform a single open-label LVL 324 mg administration as the rescue therapy. METHODS: The primary efficacy endpoint was the proportion of patients with sustained clinical improvement on the 7-category ordinal scale on Day 14. All efficacy data obtained after rescue therapy administration were considered missing. For primary efficacy analysis, all subjects with missing data were considered non-responders. RESULTS: 63.1% and 42.7% of patients in the LVL and in the placebo groups, respectively, achieved sustained clinical improvement on Day 14 (P = .0017). The frequency of adverse drug reactions was comparable between the groups. CONCLUSION: In patients with radiologically confirmed SARS-CoV-2 pneumonia, requiring or not oxygen therapy (but not ventilation) with no signs of other active infection administration of LVL + SOC results in an increase of sustained clinical improvement rate. TRAIL REGISTRATION: The trial is registered at the US National Institutes of Health (ClinicalTrials.gov; NCT04397562).

Efficacy and Safety of Netakimab, A Novel Anti-IL-17 Monoclonal Antibody, in Patients with Moderate to Severe Plaque Psoriasis. Results of A 54-Week Randomized Double-Blind Placebo-Controlled PLANETA Clinical Trial.

INTRODUCTION: Netakimab (NTK), an original humanized anti-interleukin-17 monoclonal antibody, showed therapeutic efficacy in moderate-to-severe plaque psoriasis in a phase 2 clinical study. Herein we report the results of 54 weeks of a phase 3 PLANETA trial aimed to evaluate the efficacy and safety of two NTK regimens vs. placebo. METHODS: Two hundred thirteen patients with moderate-to-severe plaque psoriasis were randomly assigned to receive NTK 120 mg once every 2 weeks (NTK Q2W), NTK 120 mg once every 4 weeks (NTK Q4W) or placebo. During the first 3 weeks, patients received subcutaneous injections of NTK or placebo (according to the allocation) once a week. Patients in the NTK Q2W group then received NTK at weeks 4, 6, 8 and 10. Subjects in the NTK Q4W group received NTK at weeks 6 and 10 and placebo at weeks 4 and 8. Patients in the placebo group received placebo injections at weeks 4, 6, 8 and 10. Treatment was unblinded at week 12. During the open-label phase, patients in both NTK groups continued to receive NTK Q4W. The primary efficacy endpoint was the proportion of patients in each group who achieved a ≥ 75% reduction from baseline in psoriasis area and severity index (PASI 75) at week 12. RESULTS: A total of 77.7%, 83.3% and 0% of patients had a PASI 75 response at week 12 in the NTK Q2W, NTK Q4W and placebo groups, respectively (P < 0.0001, Fisher's exact test, ITT). The effect was maintained throughout the 1-year treatment. NTK showed a good safety profile and low immunogenicity. CONCLUSION: Treatment with NTK results in high rates of sustained clinical response in patients with moderate-to-severe plaque psoriasis. The study is ongoing; thus, long-term use efficacy and safety data are forthcoming. CLINICAL TRIAL REGISTRATION: The trial is registered at the US National Institutes of Health (ClinicalTrials.gov; NCT03390101).